SharePoint for Pharma - A Risk-Based Validation Approach for Life Sciences


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SharePoint for Pharma - SharePoint & 21 CFR Part 11

A Risk-Based Validation Approach for Life Sciences.

Presented by Paul Fenton, President & CEO of Montrium Inc.

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SharePoint for Pharma - A Risk-Based Validation Approach for Life Sciences

  1. 1. SharePoint for Pharma -SharePoint and 21 CFR Part 11A Risk-Based Validation Approachfor Life SciencesPresented byPaul FentonVP Pharmaceutical Processesand TechnologyApril 23rd COPYRIGHT MONTRIUM 2009
  2. 2. SharePoint for Pharma Series• Webinar series that aims to highlight the different aspects of validating and using SharePoint in GxP environments• Should provide attendees with a good grounding for their SharePoint projects• Slides can be distributed upon request. Details on how to request slides will be distributed to attendees following each webinar• Feel free to ask questions in the questions panel• Thank you for your interest! COPYRIGHT MONTRIUM 2009
  3. 3. Overview• Objectives of validation• Regulatory requirements• How to identify electronic records• Deploying controlled and non-controlled MOSS environments• Risk evaluation methods and scoping the validation strategy• Step by Step overview of the risk-based validation process following the GAMP5 model• Implementing effective configuration and change control procedures for MOSS• Maximizing quality and ROI• Lessons learned and best practices• Upcoming COPYRIGHT MONTRIUM 2009
  4. 4. What is Computer Systems Validation?• A formal process to ensure that: • systems consistently operate as they were intended • user, business and regulatory system requirements are met • information is secure and properly managed by the system • procedures and processes are in place for the use and management of the system COPYRIGHT MONTRIUM 2009
  5. 5. What the regulations say… • FDA: 21 CFR Part 11 §11.10(a) Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records. • ICH E6 – GCP §5.5.3(a) Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability and consistent intended performance (i.e. validation) COPYRIGHT MONTRIUM 2009
  6. 6. What the regulationssay…. • FDA: CSUCI §F5 Change Control - The integrity of the data and the integrity of the protocols should be maintained when making changes to the computerized system, such as software upgrades, including security and performance patches, equipment, or component replacement, or new instrumentation. The effects of any changes to the system should be evaluated and some should be validated depending on risk. Changes that exceed previously established operational limits or design specifications should be validated. Finally, all changes to the system should be COPYRIGHT MONTRIUM 2009
  7. 7. Other important guidance documents• PIC/S Annex 11 – PI 011-3 Good Practices for Computerised Systems in Regulated GxP Envrionments (2007)• US FDA: General Principles of Software Validation; Final Guidance for Industry and FDA Staff (2002) COPYRIGHT MONTRIUM 2009
  8. 8. What is expected?• That procedures should be in place to ensure that systems used in regulated activities are adequately validated• That systems should be maintained in a validated state through effective change control mechanisms• That sponsors take a risk based approach to computer systems validation (CSV)• That individuals involved in CSV activities and the maintenance of validated systems have adequate experience and training COPYRIGHT MONTRIUM 2009
  9. 9. How to identify electronic records• 21 CFR Part 11 defines electronic records as: • Records that are required to be maintained under predicate rule requirements and that are maintained in electronic format in place of paper format • Records that are required to be maintained under predicate rules, that are maintained in electronic format in addition to paper format, and that are relied on to perform regulated activities COPYRIGHT MONTRIUM 2009
  10. 10. How to identify electronic records• 21 CFR Part 11 defines electronic records as: • Records submitted to FDA, under predicate rules (even if such records are not specifically identified in Agency regulations) in electronic format • Electronic signatures that are intended to be the equivalent of handwritten signatures, initials, and other general signings required by predicate rules COPYRIGHT MONTRIUM 2009
  11. 11. Electronic Records within MOSS• Records within the context of MOSS could be: • Documents (excluding descriptive metadata) required to be maintained by predicate rule • Metadata (Columns) used to perform regulated activities (or make regulated decisions) • InfoPath forms used to document regulated COPYRIGHT MONTRIUM 2009
  12. 12. Electronic Records within MOSS • Electronic / Digital Signatures used to sign records required by predicaterules • Audit Trails generated for electronic records being generated and/or managed in COPYRIGHT MONTRIUM 2009
  13. 13. How to identify electronic records• Points to consider: • Does the record exist in electronic format only with no paper source? • Is the record required by predicate rule? • Does the record drive a regulated process or decision?• If the answer to any of the above is ‘Yes’ then 21 CFR Part 11 applies and your system must be validated• You should document this in a validation assessment document or validation plan. You should also clearly identify the scope of validation in this document• This document can help structure your MOSS deployment into controlled and non-controlled COPYRIGHT MONTRIUM 2009
  14. 14. Controlled vs. Non- Controlled MOSS Architecture• MOSS can be used across the enterprise for many different applications and groups• It is imperative to make a clear separation between controlled (validated) and non-controlled environments• This can be achieved by deploying an independent web application/site collection or controlled sites for regulated documents and processes• There are advantages and disadvantages to both models due to limitations of MOSS• These architecture models aim to offer both flexibility and control and reduce validation / change control COPYRIGHT MONTRIUM 2009
  15. 15. Controlled vs. Non- Controlled – Integrated Option Central Admin •Features and Solutions (Scope must be controlled) Admin •Administered Forms (Scope must be controlled) DB •Controlled Content Types Validated Web Application •Controlled Security Groups •Controlled Columns Top Level Site Collection (Controlled)•Controlled Templates •Controlled Lists Content DB Controlled Record Center or Uncontrolled Functional Sites – Document Functional Sites Custom Validated Custom Repository –•Uncontrolled Content Types Send-To / Hyperlinks Send-To / Validated•Uncontrolled Columns Hyperlinks•Uncontrolled Lists•Uncontrolled Security Groups •Controlled Site and Library •Information Management•Uncontrolled Templates structures Policies•Non-validated Features and •Validated Features and •Records Mgt Site StructuresSolutions Solutions •Record Mapping•Non-validated Workflows • Validated Workflows • Validated COPYRIGHT MONTRIUM 2009
  16. 16. Controlled vs. Non- Controlled – Isolated Option Central Admin •Features and Solutions (Scope must be controlled) Admin •Administered Forms (Scope must be controlled) DB Uncontrolled Web Validated Controlled Web Application Application •Controlled Content Types •Controlled Security Groups •Uncontrolled Templates •Controlled Columns •Controlled Templates •Uncontrolled Content Types •Controlled Lists •Uncontrolled Columns Content •Uncontrolled Lists DB •Uncontrolled Security GroupsContent Controlled Record Center or DB Functional Sites – Document Uncontrolled Validated Custom Send-To / Repository – Functional Sites Hyperlinks Hyperlinks Validated •Non-validated Features and •Controlled Site and Library •Information Management Solutions structures Policies •Non-validated Workflows •Validated Features and •Records Mgt Site Structures Solutions •Record Mapping • Validated Workflows • Validated Dashboards COPYRIGHT MONTRIUM 2009
  17. 17. Example of Controlled and Non-Controlled Environment Central Admin / TLS Uncontrolled Controlled Workspace Workspace RegOps RecordsClinOps PV CMC HR ClinOps PV CMC RegOps Center Validated Environment COPYRIGHT MONTRIUM 2009
  18. 18. Risk Evaluation and Scoping the Validation Strategy• Agencies are actively encouraging the use of risk based approaches for the validation of computerized systems used in GxP environments• The use of a risk based approach allows us to focus on high risk areas whilst reducing the validation effort and improving quality• When starting the deployment of MOSS in regulated environments, it is important to evaluate risk so as to focus validation efforts on high risk areas• Risk should be measured at two levels: • General procedural risk • Detailed functional risk COPYRIGHT MONTRIUM 2009
  19. 19. Risk Evaluation and Scoping the Validation Strategy• Risk can be identified as either regulatory risk or business risk• You should clearly specify that you intend to adopt a risk based approach in your validation plan and also explain the rationale behind the approach• Ensure that risk assessment is carried out by a knowledgeable team• Be strict as everything can end up being high-risk with enough debate… COPYRIGHT MONTRIUM 2009
  20. 20. Risk based approach 101 – Identify Scope• Step 1 - When defining the scope of your MOSS deployment clearly identify regulated procedures and records that will be generated or managed by the system MOSS Examples: 1. MOSS will be used to generate submission ready electronic PDF records that will be submitted to FDA as part of our INDs 2. MOSS will be used to control the drug shipment authorization process for clinical sites 3. MOSS will be used to generate CAPA records for our GMP facility 4. MOSS will be used to manage audit report observationsIMPORTANT: If MOSS will not be used for processes or records that are governed by predicate rules…there is no regulatory requirement to validate! COPYRIGHT MONTRIUM 2009
  21. 21. Risk based approach 101 – Risk Type / GxP Determination• Step 2 - Associate a type of risk (regulatory or business) to each record or process based on the following criteria: A. Is the record or procedure governed or required by predicate rule? B. Does the procedure or record have an impact on subject safety? C. Does the procedure or record have an impact of product quality? D. Does the procedure or record have an impact on data integrity? E. Does the procedure or record have a important impact on our ability to carry out the daily tasks of our business? MOSS Examples: 1. MOSS will be used to generate submission ready electronic PDF records that will be submitted to FDA as part of our INDs – Regulatory risk (A) 2. MOSS will be used to control the drug shipment authorization process for clinical sites – Regulatory Risk (B) 3. MOSS will be used to generate CAPA records for our GMP facility – Regulatory Risk (C) 4. MOSS will be used to manage audit report observations – Regulatory and Business Risk (A-E) IMPORTANT: If a procedure or record has no regulatory risk associated, it may be excluded from the validation effort provided that adequate rationale is provided COPYRIGHT MONTRIUM 2009
  22. 22. Risk based approach 101 – Risk Scenarios• Step 3 – Define risk scenarios for each process or record identified. Scenarios should include: • Potential risk • Likelihood of occurrence/detection • Impact • Palliative actions MOSS Example: 1. MOSS will be used to control the drug shipment authorization process for clinical sites – Regulatory Risk (B) Risk Scenario A: • Risk: IRB approval has not been received and a subject is enrolled in study and treated • Likelihood: Medium – Due to combination of procedural and system controls • Impact: High – Treating subjects without IRB approval considered a serious deviation • Palliative Action: Ensure that drug cannot be shipped to site before IRB approval has been received through system and procedural controls COPYRIGHT MONTRIUM 2009
  23. 23. Risk based approach 101 – Link System Functions to Scope• Step 4 – Once processes and records have been classified by procedural risk, they must be linked to the system functionality defined in the user requirements specification (URS): MOSS Example: Process / Record URS ID Requirement MOSS will be used to UR3.1. The system should allow the automatic generation of generate submission PDF v1.4. files ready electronic PDF UR3.2. The system should allow the electronic signature of records that will be records submitted to FDA as part of our INDs UR3.3. The system should be able to invalidate electronic signatures if the signed record is modified UR3.4. The system should manage the version number of records UR3.5. The system should be capable of rendering final records read-only COPYRIGHT MONTRIUM 2009
  24. 24. Risk based approach 101 – GAMP Risk Evaluation method Probability Detectability Medium Medium High High Low Low Risk Class 2 1 1 M H H Risk Class Priority Severity High 1 Risk 3 2 1 Medium L M H 2 Low 3 3 2 3 L L M M Severity = Impact on Patient Safety, Detectability = Likelihood that the Product Quality or Data Integrity fault is detected before harm Probability = Likelihood of fault occurs occurring Priority = Risk Class xDetectability Risk Class = Severity x COPYRIGHT MONTRIUM 2009
  25. 25. Risk based approach 101 – Decide on risk acceptability level• Step 5 – Based on the type of system and the high level risk assessment we must decide on what level of risk must be tested for during validation • Custom built systems or components tend to present a higher level of risk than OTS systems • It may be appropriate to exclude business risk from testing • The validation plan should specify the acceptable risk levels with rationale MOSS Example: 1. All OTS MOSS functions that have a risk rating of low or medium will not be formally tested during validation. These functions are deemed to be adequately tested by the vendor. 2. All custom applications deployed within the MOSS environment that have GxP impact and a risk rating of medium or high will be formally tested during validation. Low risk functions and functions that do not have GxP impact will be informally verified during the build COPYRIGHT MONTRIUM 2009
  26. 26. Risk based approach 101 – Evaluate System Functions • Step 6 – Once processes and records have been linked to system functions, a risk evaluation of each function involved is undertaken:MOSS Example: Process / URS Requirement Risk Scenario Severity / Test Record ID Probability / Y/N Detectability Low (L), Medium (M), High (H) MOSS will UR3.1 The system should allow PDF Files are be used to . the automatic generation generated in M L H No L generate of PDF v1.4. files the incorrect submission format ready electronic UR3.2 . The system should allow the electronic signature of Record cannot be signed L M H No L PDF records records that will be submitted UR3.3 The system should be Signature to FDA as . able to invalidate remains valid H M L Yes H part of our electronic signatures if after record INDs the signed record is modification modified COPYRIGHT MONTRIUM 2009
  27. 27. Risk based approach 101 - Completion• The result of the functional risk assessment provides us with the foundation for the various tests that we should execute against the installed MOSS environment• The same methodology should be applied when performing change control• Risk assessment should be reviewed by the system stake holders and QA for completeness before moving on to the next step of COPYRIGHT MONTRIUM 2009
  28. 28. Step by Step CSV Model• GAMP5 is a standard that was established by ISPE• The standard provides a framework for achieving compliant GxP computerized systems• This standard is widely recognized and understood by industry• GAMP provides guidance for the validation of different categories of systems• MOSS would be considered a Configured Off the Shelf system within the context of GAMP• It is expected that these systems have already undergone significant validation during development by the vendor• Configured off the shelf systems require less validation effort than customized COPYRIGHT MONTRIUM 2009
  29. 29. GAMP5 – CSV Framework for a Configured Product Responsibility: User Sponsor Requirements Requirements Specification Testing (PQ) Functional Functional Specification Testing (OQ) Configuration Configuration Specification Testing (IQ) Configured Product Supplier QMS COPYRIGHT MONTRIUM 2009
  30. 30. CSV Documents – Validation Plan• Governs the validation process for a system• Outlines: • Roles and responsibilities • Validation approach and risk rationale • System scope and pre-requisite requirements • Documentation deliverables for the system• The plan should be high level and flexible whilst clearly specifying what is required to achieve compliance• If MOSS is to be deployed in a controlled and non- controlled configuration, the plan should clearly state that only the controlled environment will be validated COPYRIGHT MONTRIUM 2009
  31. 31. CSV Documents – User Requirements Specification • Document that defines: • business (end user) requirements • functional requirements • performance requirements • regulatory requirements (including 21 CFR Part 11 requirements) • system architecture and security requirements • Requirements should be precise and measurable • Used as the basis for developing test scripts • Try to prioritize requirements (Must, Should, Want) • Try and minimize requirements and avoid stating the obvious for known OTS systems such as COPYRIGHT MONTRIUM 2009
  32. 32. CSV Documents – Traceability Matrix• It is strongly recommended that a traceability matrix is maintained throughout the lifetime of the system• The trace matrix: • Links test scripts to user and functional requirements • Ensures that all requirements are adequately tested • Indicates the risk classification for each testable requirement • Should be considered a living document and therefore versioned and updated during change COPYRIGHT MONTRIUM 2009
  33. 33. CSV Documents – Functional Specification• Functional specifications allow us to describe how system functions will meet user requirements• The functional specification clearly describes: • The purpose of each function • The inputs • The process • The outputs• Functional specifications are not required for the installation and configuration of baseline MOSS• Functional specifications should be developed for: • Validated InfoPath forms • Validated workflows • Custom web parts, features and solutions • Integration with any third party applications or services COPYRIGHT MONTRIUM 2009
  34. 34. CSV Documents – Configuration Specification• The configuration specification clearly documents: • The baseline MOSS parameters and architecture required for installation of the product and any 3rd party add-ons • The structure of the controlled environment, notably: • Site and library settings • Libraries • Content types • Columns • Security groups and user rights • Template and workflow deployment• The specification can be versioned and used to document the execution of the configuration in MOSS• The specification should be updated each time changes are required through change control COPYRIGHT MONTRIUM 2009
  35. 35. CSV Documents – Configuration Testing (IQ)• Ensures that all software modules are installed correctly• Lists step by step process for the installation and configuration of all software modules• Defines expected results at each control point of the installation• Ensures that all documentation is in place and that the system is adequately protected• Ensures proper verification of the structural elements i.e. sites, content types etc.• It is recommended to develop an IQ protocol which governs the overall installation and configuration process• Develop IQ scripts for the installation of baseline MOSS and 3rd party add-ons in all validated environments• Develop IQ scripts for the execution of the configuration specification for structural MOSS elements COPYRIGHT MONTRIUM 2009
  36. 36. CSV Documents – Functional Testing (OQ)• Consists of end to end positive and negative testing that all system components i.e. hardware and software are operating as intended• Tests are executed on base functionality by end users and IT• Tests are governed by a test protocol which clearly describes the test and deviation management procedures that must be followed• Tests should be broken down into test scripts by functional area, linked to baseline system functions, and be approved before execution• All test results should be clearly documented using good documentation practices (ALCOA)• Tests serve as a mechanism to verify that the system is operating correctly in its installed COPYRIGHT MONTRIUM 2009
  37. 37. CSV Documents – Requirements Testing (PQ)• Requirements testing consists of positive testing of business specific configuration and user requirements• Tests are executed on business specific functionality such as workflows or InfoPath forms that were identified as being testable during the risk assessment exercise• Tests are governed by a test protocol which clearly describes the test and deviation management procedures that must be followed• Tests should be broken down into test scripts by process and be linked to user and functional requirements, and be approved before execution• All test results should be clearly documented using good documentation practices (ALCOA)• Tests are typically executed by end users and serve as a user acceptance mechanism COPYRIGHT MONTRIUM 2009
  38. 38. Final Validation Summary Report• Describes how the validation went, verifies that all deviations are closed, and provides for the final approval of the CSV document package to allow the system to go into production• Individual summary reports for each step of the verification process or a comprehensive report covering all steps may be produced• The summary report should clearly show that the validation plan and protocols were followed and that the acceptance criteria for putting the system into production have been COPYRIGHT MONTRIUM 2009
  39. 39. Configuration control and maintaining the validated state• Configuration control should be governed by a formal MOSS specific procedure in addition to any general provisions of the IT Configuration control SOP• This procedure should govern the update of the configuration specification• The configuration specification should be used to clearly document updates / additions to MOSS• Any changes to the validated controlled environment must also be documented using change control• Should significant changes or additions be made, a new validation project may be required• For workflows, forms or features/solutions it is imperative to correctly evaluate impact and risk and produce adequate test scripts properly integrate the additional elements into the current environment COPYRIGHT MONTRIUM 2009
  40. 40. Maximizing quality and ROI• Validation can be expensive and time consuming if it is not done correctly• By defining a clear validation strategy and by leveraging risk assessment techniques, we are able to focus the validation effort on what is really important• Consider acquiring tried and tested test scripts and/or validation packages for MOSS / third party add-ons so as to reduce the amount of preparation time and improve quality• Make sure that all individuals involved in the validation effort are fully trained and understand the CSV process• Isolated controlled environments facilitate validation and configuration control• Use virtual environments so as to facilitate replication between production and test environments COPYRIGHT MONTRIUM 2009
  41. 41. Lessons learned and best practices• Create a ‘Big Picture’ of your MOSS deployment so as to ensure that you are able to adequately accommodate all of your controlled and non-controlled needs• Use a risk based approach to focus and reduce validation efforts – be strict otherwise everything becomes high risk…• Remember that MOSS is an off-the-shelf product and that you should limit validation scope to high risk business and regulatory requirements as much as possible• Establish a MOSS validation team to oversee and manage the validation process and changes to the controlled MOSS environment• Implement SOPs and WIs which clearly define how the environment is configured and administered and which level of documentation / re-validation is required by type of change• Use a step by step deployment methodology to keep things manageable COPYRIGHT MONTRIUM 2009
  42. 42. It is easy to drown in the details… Try and keep it SIMPLE! COPYRIGHT MONTRIUM 2009
  43. 43. What’s next…• Montrium will present the second webinar in its SharePoint for Pharma series on Configuration Control of SharePoint in Regulated Environments on Friday May 7th 2010 at 11am EST• This webinar will cover:• Implementation of formal system specific configuration control procedures• Importance of defining clear taxonomies and standards across the enterprise• Configuration deployment and version control techniques• Integration with the validation and change control process• Importance of leveraging a risk based approach to QC• Using SharePoint to manage configuration control We look forward to seeing you there! COPYRIGHT MONTRIUM 2009
  44. 44. Contact Details Paul Fenton Montrium Inc. 361 St-Joseph West, Montreal (QC) H2V 2P1 Canada Tel. 514-223-9153 ext. 206 You can also find me on LinkedIn… COPYRIGHT MONTRIUM 2009